A RNA Interference Screen Identifies the Protein Phosphatase 2A Subunit PR55γ as a Stress-Sensitive Inhibitor of c-SRC

Protein Phosphatase type 2A (PP2A) represents a family of holoenzyme complexes with diverse biological activities. Specific holoenzyme complexes are thought to be deregulated during oncogenic transformation and oncogene-induced signaling. Since most studies on the role of this phosphatase family have relied on the use of generic PP2A inhibitors, the contribution of individual PP2A holoenzyme complexes in PP2A-controlled signaling pathways is largely unclear. To gain insight into this, we have constructed a set of shRNA vectors targeting the individual PP2A regulatory subunits for suppression by RNA interference. Here, we identify PR55γ and PR55δ as inhibitors of c-Jun NH₂-terminal kinase (JNK) activation by UV irradiation. We show that PR55γ binds c-SRC and modulates the phosphorylation of serine 12 of c-SRC, a residue we demonstrate to be required for JNK activation by c-SRC. We also find that the physical interaction between PR55γ and c-SRC is sensitive to UV irradiation. Our data reveal a novel mechanism of c-SRC regulation whereby in response to stress c-SRC activity is regulated, at least in part, through loss of the interaction with its inhibitor, PR55γ.     

Fundamental limits to position determination by concentration gradients

Position determination in biological systems is often achieved through protein concentration gradients. Measuring the local concentration of such a protein with a spatially varying distribution allows the measurement of position within the system. For these systems to work effectively, position determination must be robust to noise. Here, we calculate fundamental limits to the precision of position determination by concentration gradients due to unavoidable biochemical noise perturbing the gradients. We focus on gradient proteins with first-order reaction kinetics. Systems of this type have been experimentally characterised in both developmental and cell biology settings. For a single gradient we show that, through time-averaging, great precision potentially can be achieved even with very low protein copy numbers. As a second example, we investigate the ability of a system with oppositely directed gradients to find its centre. With this mechanism, positional precision close to the centre improves more slowly with increasing averaging time, and so longer averaging times or higher copy numbers are required for high precision. For both single and double gradients, we demonstrate the existence of optimal length scales for the gradients for which precision is maximized, as well as analyze how precision depends on the size of the concentration-measuring apparatus. These results provide fundamental constraints on the positional precision supplied by concentration gradients in various contexts, including both in developmental biology and also within a single cell.     

Lateral hydrological connectivity differentially affects the community characteristics of multiple groups of aquatic invertebrates in tropical wetland pans in South Africa

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The immunoglobulin lambda variable light-chain region in primates has been shaped by multiple, independent, small-scale and large-scale insertion/deletion events

We analyzed genomes of nonhuman primates to determine the ancestral state of a 9.1-kb insertion/deletion polymorphism, located on human chromosome 22. The 9.1-kb+ allele was found in 16 chimpanzees, 3 bonobos, and 2 Bornean orangutans; however, 9 chimpanzees and 6 Sumatran orangutans showed neither the 9.1-kb+ nor the 9.1-kb- allele, but a novel allele, termed 9.1-kbnull. A clone from a chimpanzee BAC library carrying the 9.1-kbnull allele was sequenced: the BAC DNA aligns with the human chromosome 22 reference sequence except for a 75-kb region, suggesting that the 9.1-kbnull allele originated from a deletion. Furthermore, the 9.1-kb+ chromosomes of chimpanzees and bonobos contain a 1030-nucleotide sequence, absent in humans, that may result from a retro-transposition insertion in their common ancestor. Our results provide additional evidence that human chromosome 22 has undergone multiple small-scale and large-scale insertions and deletions since sharing a common ancestor with other primates.     

Frames of reference for eye-head gaze commands in primate supplementary eye fields

The supplementary eye field (SEF) is a region within medial frontal cortex that integrates complex visuospatial information and controls eye-head gaze shifts. Here, we test if the SEF encodes desired gaze directions in a simple retinal (eye-centered) frame, such as the superior colliculus, or in some other, more complex frame. We electrically stimulated 55 SEF sites in two head-unrestrained monkeys to evoke 3D eye-head gaze shifts and then mathematically rotated these trajectories into various reference frames. Each stimulation site specified a specific spatial goal when plotted in its intrinsic frame. These intrinsic frames varied site by site, in a continuum from eye-, to head-, to space/body-centered coding schemes. This variety of coding schemes provides the SEF with a unique potential for implementing arbitrary reference frame transformations.     

Acute and specific collagen type I degradation increases diastolic and developed tension in perfused rat papillary muscle

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Vasoconstrictor effects of insulin in skeletal muscle arterioles are mediated by ERK1/2 activation in endothelium

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